Stoppage-time goals from Billy Sharp and Sander Berge ended Wrexham’s FA Cup dream and secured Sheffield United a home meeting with Tottenham.
Anel Ahmedhodzic had put the Blades ahead but Paul Mullin hauled National League Wrexham level with a penalty.
However, Mullin then saw a second penalty saved by United goalkeeper Adam Davies and breakaway goals from Sharp and Berge wrapped up a 3-1 win.
Grimsby sprung a surprise and booked a trip to Southampton after a thumping 3-0 win over Championship Luton.
Harry Clifton and Danilo Orsi put the League Two side in control and when Danny Amos launched a free-kick into the top corner on the stroke of half-time the game was up for the Hatters.
Fleetwood are through after a 1-0 win over League One leaders Sheffield Wednesday.
A header from Carlos Mendes Gomes on the hour mark sank the Owls as Town earned a fifth-round meeting with Burnley.
The Clarets secured their passage thanks to two goals from Nathan Tella, the second in stoppage time, to beat Ipswich 2-1.
In a breakneck start Tella fired Burnley ahead in the third minute but 60 seconds later Ipswich equalised through George Hirst.
However, Tella had the last word four minutes into time added on to send his side through.